Calcium homeostasis Flashcards
Roles of calcium (5)
Signalling - for exocytosis of vesicles, muscle contraction
Blood clotting - essential part of clotting cascade
Apoptosis
Skeletal strength
Membrane excitability - calcium decreases sodium permeability
What effect does hypocalcaemia have on neuronal Na+ permeability
increases Na+ permeability leading to hyper excitation of neurons
What effect does hypercalcaemia have on neuronal Na+ permeability
decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity
Percentage distribution of calcium in the body (divided into 3 places)
Bones - 99%
Intracellular (mainly stored in mitochondria and sarcoplasmic reticulum) - 0.9%
Extracellular fluid - 0.1%
0.1% calcium in the body is distributed in the ECF, how much of this is physiologically active
Only 0.05% as the other 0.05% is bound to carrier proteins like albumin or globulins so is not free in solution
99% of calcium in the body is distributed in bone - how is it stored in bone
in the form of hydroxyapatite, in the extracellular matrix of bone
Conc. of calcium in the plasma (i.e. ECF)
Conc. of physiologically active calcium in the plasma (i.e. free in solution)
- 2-2.6mM (av. 2.4mM)
1. 2mM (as 50% Ca2+ in ECF is unbound, therefore free and ionised)
What minerals does hydroxyapatite consist of (2)
Calcium + phosphate
0.1% calcium that is distributed in the ECF (blood) is further sub-distributed in what 3 ways
40% bound to protein
50% free in solution
10% complexed with anions, e.g. bicarbonate, phosphate, to form calcium carbonate/phosphate etc
The binding capacity of plasma proteins to Ca2+ is affected by what
pH
-binding capacity is increased under alkaline conditions
How does hyperventilation affect the binding capacity of plasma proteins to Ca2+
binding capacity is increased under alkaline conditions so hyperventilating would cause plasma proteins to bind more Ca2+ as hyperventilating means you’re breathing out more CO2 so making blood more alkaline
May lead to hypocalcaemic tetany (involuntary contraction of muscle as neuronal permeability to Na+ is increased so progressive depolarisation)
How does alkalosis increase the binding capacity of plasma proteins to calcium (acidosis therefore opposite)
in alkalosis, protons are deprotonated (i.e. loss of hydrogen ions bound to plasma protein which frees up binding spaces for Ca2+)
so the overall resulting negative charge on the protein allows Ca2+ to bind, thus reducing the amount of ionised calcium whilst total extracellular Ca2+ remains constant
whereas acidosis, there’s increased plasma hydrogen ions so they’d displace the Ca2+ bound to plasma proteins and increase the amount of free ionised Ca2+
The 99% calcium store in bone functions to provide mechanical support but function is prioritised over this
Maintaining Ca2+ balance by releasing its calcium stores into the blood when needed TO MAINTAIN 1.2mM physiologically active plasma calcium
What are osteoblasts + function
Bone building cells
-lay down collagen matrix which then calcifies into bone
What do osteoblasts differentiate into
Osteocytes when established in bone
Function of osteocytes
regulate the activity of osteoblasts and osteoclasts
- much less active than osteoblasts
What are osteoclasts + function
Bone resorbing/destructing cells
- mobilise bone to allow release of its Ca2+ stores
- —-> does this by secreting H+ to dissolve calcium salts and provide proteolytic enzymes to digest the extracellular matrix and release Ca2+ into blood
Explain the overall effect of PTH on plasma Ca2+ and phosphate concentrations
To increase concentration of free plasma Ca2+ (i.e. Ca2+ that is not bound to carrier protein)
Decreases plasma phosphate concentrations which in turn elevates free plasma Ca2+ conc. as it’s prevented from being deposited back into bone, as that process requires phosphate
What is calcitriol + what organs is it produced by
Active form of vitamin D (vitamin D3)
Steroid hormone produced from vitamin D by liver AND kidneys (first step is in liver)
Describe the 5 different mechanisms in which PTH increases free plasma Ca2+ conc.
Stimulates osteoclasts (BONE) to INCREASE RELEASE OF Ca2+ and phosphate into blood
Inhibits osteoblasts to reduce Ca2+ deposition in bone
Increases REABSORPTION OF Ca2+ from KIDNEY tubules, so decreasing its excretion in urine
Increasing RENAL EXCRETION OF PHOSPHATE, which elevates free plasma Ca2+ by preventing it from being deposited back into bone (a process that requires phosphate)
Stimulate the kidney to synthesise CALCITRIOL from vitamin D to promote calcium absorption at the gut and kidney
What relationship does calcitriol have with PTH
It complements the action of PTH to increase plasma Ca2+ conc.
In what 2 ways can be obtain calcitriol (active vitamin D3) (2)
From dietary vitamin D
UV light on skin –> activating endogenous (internal) precursors of vitamin D
Primary action of calcitriol (activated form of vitamin D by kidney) + other actions (2)
Increase Ca2+ absorption form gut by active transport form intestinal lumen into blood
Facilitates renal absorption of Ca2+
Mobilises Ca2+ stores in bone by stimulating osteoclast activity
*Goal of calcitriol is to increase plasma Ca2+ conc. like PTH
Increased levels of PTH stimulate the kidneys to release what
Calcitriol
